Urotensin II is an autocrine/paracrine growth factor for aortic adventitia of rat.
Urotensin II (UII) is a potent vasoconstrictive peptide; however, its significance in vascular adventitia has not been clearly elucidated. In this study, rat aortic adventitia showed mRNA expression and immunoreactivity of UII and its receptor (UT). Moreover, radioligand-binding assay showed that maximum binding capacity (Bmax) of [(125)I]-UII was higher in adventitia than in media (28.60+/-1.94 vs. 20.21+/-1.11 fmol/mg, P<0.01), with no difference in binding affinity (dissociation constant [Kd] 4.27+/-0.49 vs. 4.60+/-0.40 nM, P>0.05). Furthermore, in cultured adventitial fibroblasts, UII stimulated DNA synthesis, collagen synthesis and secretion in a concentration-dependent manner. These effects were inhibited by the UII receptor antagonist urantide (10(-6) mol/l), Ca(2+) channel blocker nicardipine (10(-5) mol/l), protein kinase C inhibitor H7 (10(-6) mol/l), and mitogen-activated protein kinase inhibitor PD98059 (10(-6) mol/l) but not the phosphatidyl inositol-3 kinase inhibitor wortmannin (10(-7) mol/l). UII may act as an autocrine/paracrine factor through its receptor and the Ca(2+) channel, protein kinase C, and mitogen-activated protein kinase signal transduction pathways, in the pathogenesis of vascular remodeling by activating vascular adventitia.
Zhang
Yonggang
Y
Department of Cardiovascular Diseases, First Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, China. zhangyg8686@hotmail.com
Li
Yuguang
Y
Wei
Ruihong
R
Wang
Zhijian
Z
Bu
Dingfang
D
Zhao
Jing
J
Pang
Yongzheng
Y
Tang
Chaoshu
C
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology*; D019898:Autocrine Communication; D001483:Base Sequence; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis; D003238:Connective Tissue / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006133:Growth Substances / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D019899:Paracrine Communication; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D014579:Urotensins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*
D017931:DNA Primers; D006133:Growth Substances; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D014579:Urotensins; C473142:Uts2r protein, rat; D003094:Collagen; C029677:urotensin II